Lowering blood pressure effect of Apium graviolens (seledri) and Orthosipleon stamineus benth (kumis kucing) in mild and moderate hypertension

VoL I

l,

No 4, October

-

BLood pressure and

December 20A2

traditional medicine

195

Lowering blood pressure effect of Apium graviolens (seledri) and
Orthosipleon stamineus benth (kuwîs kucing) in mild and rnoderate
hypertension
Fadilah Supari


Abstrak
Indonesia Apiurn graviolens (seledri) dan Orthosiphon stamineus benth (kumis kucing) sudah lama dikenal sebagai bahan obat
tradisional yang dipercaya dapat menurunkan telcanan darah. Pada saat ini sudah beredar di pasaran [ndonesia kemasan fitofarmaka
yang berisi kombinasi antara dLa bahan tersebut. OIeh lurena itu perlu dilalatkan penelitian untuk mengetahui efektifitas dan efek
samping terhadap penderita hipertensi ingan dant sedang. Penelitian dilakukan di daerah Monica Jakarta di Jakarta Selatan 3 Juli
ta hipertens^i ringan dan sedang dengan randomized double blind contolled tial. Kelompok
sampai 29 Oktober
(Tensigarf yang beisi seledi dan kumis kucing) sebanyak 3 x 250 mg, sedangkan kelompok
p"rto*o (72 subjek)
kedua (70 sttbjek) diberikan Amlodipine I x 5 mg. Pengamatan dilakukan selnma 12 minggu dan parameter yang diukur adalah tekanan
darah sistolik maupun diastolik kadar tipid plasmn, kadar gula darah sebelum dan sesudah perlakuan, serta kndar elekrrolit tiap dtta
minggu perlahnn. Hasil penelitian menunjuklam bahwa pemberian ftofarruka selama dua belas minggu menurunlcan telanan darah
sistolik (TDS) maupun diastolik (TDD) setara dengan Amlodipine (TDS 24,72 ! 1.63 mmHg vs 26,27 + 2.18 mmHg, P > 0,05; TDD
10,00 t 0.96 mmHg vs 9,49 t 1.37 mmHg P > 0.05). Di sarnping itu pemberian ftofarmal 0.05). Phytopharmaca treatment for 12 weel 0.050 based on the results of significant
statistical tests. AII statistical tests were based on two
tail tets. All caculation were performed by using SPPS
software version 10.

Table 1. Some characteristics of subjects


Phytopharmaca Amlodipine

(N=72)

0.922

Maie

54

52

Female

t8

18

No


38

40

Yes

34

30

No

29

40

Yes

43


30

No

29

45

Yes

43

18

6Z

63

Smoking habits


participated in this study tbr each groups. During the
study period there were 18 subjects discontinued the
study (eight subjects from the phytopharmaca group,

and 10 subjects belonged to Amlodipine

group).
discontinuing this

0.1

Family history

Diabetes

mellitus type

l7

0.423


0.414

II

No

'l

10

Yes

Table

2.

Some characteristics ofsubjects

Phyopharmaca Amlodipine


(N=72)
SD

Mean +

Height (cm)
Blood pressure on entry
Systolic (mmHg)
Diastolic (mrnHg)

t.26

0378

61.40r r.32

6l.t8J

1.47


0.913

157.48 + 0.85

t58.72+

163.68

+

+

1.05

1.64

96.67 + 0.77

Laboratory (mg/dl)

Total cholesterol

reasons.

205.81 + 4.66

4t.62+

HDL
LDL

r31.07+4.35

Triglyceride

164.00 + 8.29

Fasting blood sugar

101,99 + 3.76


SGOT

20.96

SCPT

2325+ t.66

Electrolytes (mmoUdt)
Kalium

1.47

+ 1.00

4.53 + 0.08
ro4.59

Chloride


t0

42

2 l3 + 0 06

Magnesium

t40.98 + 0.26

Natrium

(N=70)
Mean + SD

61.03t

59.60

Physical performance
Body weight (kg)

There were several reasons for
study, such as: (l) The subjects could not afford the
side effect; (2) The subjects felts that the medicines
were not suitable; (3) The subjects moved to other
address and could not be followed-up; (4) Other
Table I shows that phytopharmaca and Amlodipine
groups were similarly distributed with respect to
gender, smoking habits, family history. Furthermore,
more phytopharmaca group than Amlodipine group
who had dislipidemia (P = 0.117).

0.600

Dislipidemia

Age (years)

At the beginning of the study eighty subjects

(N=70)

Gender

Ethical Committee of the National Cardiac Center
Harapan Kita approved this study.
RESULTS

197

0.9'7

0.340

t65.76+2.04

0460

96.69

0.825

+

t.t8

4.29 0.090
t.39 0.971
120.08 + 3.32 0.033
186.54 + 17.3 0.270
105.29 + 4.83 0.455
2I ;77 + 0 88 0.254
22.35 + 2-t3 0.9't9
196.06 +

42.02+

4.53+010 0.28'7
0.48 0.714
2.11+005 0.860
140.88 + 0.28 0794
104.07 +

electrolytes findings. Tensgard@ group had a significantly

Table 3 and Table 4 show that diastolic and systolic
blood pressure gradually decreased in both groups.
Systolic and diastolic blood pressure were prominent
different decreases between two groups were noted

(P = 0.033).

respectively).

In addition Table 2 shows that the two groups were
also similarly distributed with respect of age, blood
pressure on entry, laboralory (except for LDL), and
higher LDL level compared with Amlodipine group

during week

of 4

and

6 (P =

0.027 and 0.078

'!

I
I

198

Supari

Table

Med J Indones

3.

Systolic blood pressure on entry and the decrease by week of treatment

72)
from
the entry

Amlodipine (N = 70)

Phytopharmaca (N =
Systolic blood
Week

pressure

Decrease

Systotic

blood

measurement
Mean + SD

Week 0

163.68 + 1.64

Week 2

149.51+ 1.90

Week 4

149.79

Week 6

t43.54

r

Mean + SD

t
!

1.60

r3.89

20.t4

t.79

20.90

t

+ 1.14
139.i5 + 1.18

22.99

Week

8

Week

l0

140.69

Week

12

Tabte

4. Diastolic blood

N1ean

+ SD

149.41!2.30

*

Mean

SD

0.433

!

t.79

0.027

0.180

!r.39

24.49 + 1.9'7

0.220

+

1.53

25.42 + 2.t3

0.371

139.49 !1.',73

26.2'7 + 2.18

0.563

146.02

t.78

14t.67

2.08

t41.27

!1.'t3

140.34

24:12 + t.63

! t.96
tt.6l

16.36 + 2.05

23.83 t2.11

1.86

19.7 5

pressure on entry and the decrease by week of treatment

Amlodipine (N = 70)

Phytopharmaca (N = 72)
Week

the entry
measurement

165.76 + 2.04
14.17 È 1.88

1.36

!
t42.78 !

Decrease tiom

pressure

Diastolic blood
pressure

Decrease from

enty

the

blood Decrease from
pressure ' the entry

Diastolic

meâsurement
Mean + SD

Mean + SD

Week 0

96.67 + 0.71

Week 2

91 .39

Week 4

91.04

Week 6

89.10 + 0.81

Week 8

88.26

+

Week 10

87 .22

+ 0.62

9.44

Week 12

86.76

!0.82

10.00

t 0.86
t 0.87
1.06

t

Mean +

SD

0.99

91.27

+

!1.09

1.09

88.05

+

7.57

+

0.98

86.58

+

r 0.88

8.40

1.06

t

+

Mean

t

SD

96.69 +1.18

5.63

5.28

measurement

0.89
0.96

Among phytopharmaca subjects, at the end of lhe
study systolic blood pressures lhe average decreased
was 24.72 mrnHg. This is almost the same figure
among Amlodipine subjects (26.27 mmHg). The same
decreases were also noted for diastolic blood
pressures. These means both drugs were suitable to
control mild and moderate hypertension. It can be
concluded that there was no difference belween
phytopharmaca and Amlodipine to control mitd and
moderate hypertension.

Table 5 indicates that there were no significant
changes in term of laboratory findings on electrolytes,

1.18

5.42+ t.t1

0.924

8.64

0.078

+ 1.33
10.17 + 1.18

t 0.89
86.61 t 0.99

10.08

87.20 + 0.88

9.49

86.78

9.92+

r

+

1.39

0.090
0.381

1.36

0.685

t.37

0.7 56

plasma lipids, and fasting blood sugar between at the
entry and at the end of the study on both groups.
Table 6 shows that the most frequent side effect was

dizziness. For each groups revealed there were 14
(197o) subjects who experience of having dizziness.
The other side effects were considered to be rare, and
the was no significant difference between two groups.
There was one subject who Cevelops TLA, (Temporary
lschemic Attack) among Tensgard@ group. In addition,
there was noted one subject among Amlodipine group
who experience of having unstable angina. Ihe two
cases could be managed by nitrate treatments.

Vol I l, No 4, October

-

Blood pressure antl traditional

December 2002

medicine

199

Table 5. Change of electrolyte, plasma lipid, and fasting blood sugar
Phytopharmaca
On
4.53

Kalium
Magnesium

Natrium
Total cholesterol

HDL
LDL
Triglyceride
Fastins blood su

6.

The end
0.08

0.42
i
0.06
2.13
140.98 + 0.26
205.81+ 4.66
4t.62+ t.47
13t.0 t 4.35
164.00 + 8.29
t0r.99 t 3.76
t04.59 +

Chloride

Table

r

(N=72)
4.17

r

0.06

+ 0.33
2.14t 0.03

103.89

Amlodipine (N=70)
On

+ 0.10
104.07 + 0.48
2.11i 0.05
4.35

t 0.25 140.88 t 0.28
5.54 196.06+ 4.29
42.02t1.39
42.33 + 1.22
145.46+ 4.98 120.08 + 3.32
139.64 + 7.81 186.54 + 17.30
106.19 i 4.30 105.29 +4.83

The end
4.07

!

104.06
2.16

0.0'l

+

r

t

141.50

141.58

203.79!
42.851

Some side effects

133.12
152.77
108.46

0.26
4.39

0.643

1.58

0.935

0.03

215j5+

!

0.782
0.314
0.469
0.92'l

0.29

3.79

0.797

+ 13.19

0.523
0.864

t

4.09

Apiosæglukosa-

Phytopharmaca AmlodiPine

(N=72)

(N=70)

P

Dizziness
Faint

t4

14

J

1

0.934
0.324

Libido decrease
Tibial edema

I

I

0.984

0

0

Flushing on lace

I

0

0.322

Nausea

1

4

0.162

Frequent urinating

0

0

Sleepy

I

2

0.543

Tachycardia
Bradicardia

2

2

0.9'17

0

0

,r,*o#'ËHn""l
DISCUSSION

s?ledri f.or 74Vo and extract of Orthosiphon stamineus
(kumis kucing) for llVo, and added with lactose,

Phytopharmaca is a development of traditional medicine.
The basic difference between traditional medicine and
phytopharmaca is the active chemical component on
phylopharmaca is quantitatively known, whereas on the
iraditional medicine the only known is source of extract'6

magnesium stearat, and texaPon.

Furthermore, the other important things on phytopharmaca there are phase I, II, and III clinical trial
evidence. On the other hand, the traditional medicine is

Apium graviolens leaf contains atsiri o1l, protein, calcium, phosphate salt mineral, vitamin A, B and C. The
stick leaf of and the seed contain apiin and apigenin.s

One capsule of Tensigard@ consisted of active
substance of apigenin for 11.04 mg and Orthosiphon

based on empiricâl experiences or desceridence belief.

stamineus benth 8.4 mg.

In this study the phytopharmaca is a

Previous reportss'tO apigenin has an effect for aorta
vasorelaxation or vasodilalation among isolated rats
by mechanism contraction inhibition by means of

domestic

Indonesian product by gathering traditional medicines
to be a created phytopharmaca named "Tensigard@ ".
In fact this phytopharmaca has been available in the
markel as a traditional medicine Çamu)- This
phytopharmaca needs a clinical trial.

Tensigard@ is a phytopharmaca consisted of exlract of

Apium graviolens or in Indonesian language is called

.ul"iu-

released (calcium antagonist),e-r0 The other
report6 reported that apigenin has an effect to inhibit
protein kinase C or has an effect protein Kinase-C
inhibitor on rat aorta. This inhibition of cyclic
nucleotide phospo-diesterase decreases calcium
release.

ll

200

Supari

Med J Indanes

Therefore, apigenin has been proved to have a similar

Even though the phytopharmaca contains diuretics, it

effect with Calcium channei bloker.e-rt Vy'hereas,
Orthosiphon stamineus extiact contains Methylripariochromene p (MRC). The MRC has a vasodilato effect, lowering cardiac output. In addition it
has a iuresis efect.'' This effect is similar with beta

is not proved that hypokalemia occurred on the
phytopharmaca treatment. This means that the
predicted the eft'ect of calcium antagonist was more
dominant compared with diuretic effect. In addition,
the plasma lipid leveis as well as blood sugar level did

blocker efect.r2 Therefore, the phytopharmaca has a
similar effect with calcium channel blocker, a mild
beta blocker and diuretic. These three effects are
Iowering blood pressure. This study reveals that
systolic as well as diastolic blood pressures for both
groups (phytopharmaca and Amlodipine) decreased,

not change significantly.
This study noted that on both groups when SBP blood
reached 130-140 mmHg and DBP reached 90 - 80
mmHg, even though the treatment were continued,
there was drastic blood pressure decrease or
hypotension. The combination effect of calcium

and there was no significant difference.

The slope of systolic and diastolic blood

blocker, beta-blocker and mild diuretic for The
phytopharmaca seems to be tolerated to decrease
blood pressure in accordance with Amlodipine.

pressure

decreased among phytopharmaca was not as sharp as
the Amlodipine group. However, it reached significant
results at week 12. This means that phytopharmaca is
relevant to control mrld and moderate hypertension.

In

conclusion, this trial revealed that the phytopharmaca, which conlains Apium graviolens and
Orthosiphon stamineus benth, lowered systolic and
diastolic blood pressure equivalent with Amlodipine
among mild and moderate hypertensive subjects.

Diuretic effect for this phytophurmucu"-''t was not
prominent. There was no diuretic complaint from ihe
study subjects. In addition, there was no diuresis
effect toward blood electrolyte profiles. The sàme
results were also noted for plasma lipidsla'15 Eft'ect on
plasma lipids is similar with the previous report on
rats.15 The phytopharmaca had no significant effects
on blood sugar. This means there would be nor

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6.

hospitalization and he had heparinization and nitrate
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8

fitty year-old male, heavy smoker and had
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